The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

Morten Petersen; Jon T Andersen; Espen Jimenez-Solem; Kasper Broedbaek; Brian R Hjelvang; Trine Henriksen; Erik Frandsen; Julie Lyng Forman; Christian Torp-Pedersen; Lars Køber; Henrik Enghusen Poulsen

doi:10.1111/j.1440-1681.2012.05736.x

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

Morten Petersen, Jon T Andersen, Espen Jimenez-Solem, Kasper Broedbaek, Brian R Hjelvang, Trine Henriksen, Erik Frandsen, Julie Lyng Forman, Christian Torp-Pedersen, Lars Køber, Henrik Enghusen Poulsen

6 Citationer (Scopus)

Abstract

A gene-drug interaction has been indicated between β₁-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P < 0.001), whereas in Arg/Gly and Arg/Arg subjects metoprolol concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.

Originalsprog	Engelsk
Tidsskrift	Clinical and Experimental Pharmacology and Physiology
Vol/bind	39
Udgave nummer	9
Sider (fra-til)	779-785
Antal sider	7
ISSN	0305-1870
DOI	https://doi.org/10.1111/j.1440-1681.2012.05736.x
Status	Udgivet - sep. 2012

Adgang til dokumentet

10.1111/j.1440-1681.2012.05736.x

Citationsformater

Petersen, M., Andersen, J. T., Jimenez-Solem, E., Broedbaek, K., Hjelvang, B. R., Henriksen, T., Frandsen, E., Forman, J. L., Torp-Pedersen, C., Køber, L., & Poulsen, H. E. (2012). The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment. Clinical and Experimental Pharmacology and Physiology, 39(9), 779-785. https://doi.org/10.1111/j.1440-1681.2012.05736.x

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment. / Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen et al.
I: Clinical and Experimental Pharmacology and Physiology, Bind 39, Nr. 9, 09.2012, s. 779-785.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Petersen, M, Andersen, JT, Jimenez-Solem, E, Broedbaek, K, Hjelvang, BR, Henriksen, T, Frandsen, E, Forman, JL , Torp-Pedersen, C , Køber, L & Poulsen, HE 2012, 'The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment', Clinical and Experimental Pharmacology and Physiology, bind 39, nr. 9, s. 779-785. https://doi.org/10.1111/j.1440-1681.2012.05736.x

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title = "The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment",

abstract = "A gene-drug interaction has been indicated between β1-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P < 0.001), whereas in Arg/Gly and Arg/Arg subjects metoprolol concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.",

author = "Morten Petersen and Andersen, {Jon T} and Espen Jimenez-Solem and Kasper Broedbaek and Hjelvang, {Brian R} and Trine Henriksen and Erik Frandsen and Forman, {Julie Lyng} and Christian Torp-Pedersen and Lars K{\o}ber and Poulsen, {Henrik Enghusen}",

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language = "English",

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journal = "Clinical and Experimental Pharmacology and Physiology",

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T1 - The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

AU - Petersen, Morten

AU - Andersen, Jon T

AU - Jimenez-Solem, Espen

AU - Broedbaek, Kasper

AU - Hjelvang, Brian R

AU - Henriksen, Trine

AU - Frandsen, Erik

AU - Forman, Julie Lyng

AU - Torp-Pedersen, Christian

AU - Køber, Lars

AU - Poulsen, Henrik Enghusen

PY - 2012/9

Y1 - 2012/9

N2 - A gene-drug interaction has been indicated between β1-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P < 0.001), whereas in Arg/Gly and Arg/Arg subjects metoprolol concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.

AB - A gene-drug interaction has been indicated between β1-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P < 0.001), whereas in Arg/Gly and Arg/Arg subjects metoprolol concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.

U2 - 10.1111/j.1440-1681.2012.05736.x

DO - 10.1111/j.1440-1681.2012.05736.x

M3 - Journal article

C2 - 22703382

SN - 0305-1870

VL - 39

SP - 779

EP - 785

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

IS - 9

ER -

The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

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